Experimental toxic liver damage and hepatic plasma clearance of 99mTc-mebrofenin (iminodiacetate derivative). I. Early, acute CCl4-induced liver damage in rabbits.

Abstract

Liver damage was induced in rabbits by graded doses of carbon tetrachloride. The damage was assessed by means of quantitative morphometry using necrosis and steatosis of the parenchyma as end points. Biological response was measured utilizing a series of typical biochemical indices of liver damage as well as plasma clearance by the liver 99mTc-mebrofenin (an IDA derivative) and quantified indices of uptake and organ transfer of the compound. No correlation was found between the CCl4 dose and its effect (i.e. degree of necrosis and steatosis of liver). However, a very strong negative correlation was found between the degree of necrosis in individual animals and value of the clearance. The extent of the damage was positively correlated with liver transfer rate of 99mTc-MBF. Plasma activity of ALAT, TG, GGTP and AspAT were higher in the poisoned animals, however, only increments of activity of GGTP, ALAT and LDH showed statistically significant correlation with the individually assessed damage (necrosis).